Evaluation of research effort, such as estimation of the proportion of treatment successes in clinical trials, has important ethical, scientific, and public policy implications. Researchers, policymakers, funding agencies, and the public share a common interest in knowing the payback on the investments made in the research efforts for the treatment and prevention of cancer. This is particularly important for randomized controlled trials (RCTs), widely considered the most reliable method for assessing differences between effects of health care interventions. This proposal aims to answer the question how many successful new treatments, as a proportion of testing in RCTs, will ultimately be discovered. Our previous research using data from the US NCI cohort of RCTs, indicated that new treatments will be successful about 25% to 50% of time. We have hypothesized that this proportion of treatment success is not accidental, but is a direct consequence of the underlying ethical principle of equipoise, which has been advocated as a central ethical principle guiding the conduct of RCTs. If this indeed is the case, then we would appear to have described the fundamental process (dubbed as the "principle or a law of clinical discovery") which can predict efficiency of our current system of RCTs at generating clinical discoveries. However, it is not known if the success rate would be similar or if the "equipoise hypothesis" will hold true in other cohorts of RCTs. In addition, there have been claims that the process of drug development in publicly and industry-funded clinical research is different, and that industry sponsored RCTs have a better success rate due to better knowledge of their drugs. Therefore, further testing of the "equipoise hypothesis" should be done by first analyzing a new cohort of the trials sponsored by another public agency, and if the results corroborate our preliminary research, we should then pursue further analysis of industry-sponsored RCTs. To address our hypothesis, we have formulated the following specific aims: Aim 1: what is the success rate of cancer treatments in a cohort of publicly funded cooperative group, namely National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG), the second largest cohort of publicly sponsored trials in North America. The second aim of this study is to assess the robustness of the results by accounting for the factors that can affect the results, other than the true differences between the effects of treatments, such as publication rate (bias), methodological quality, and the choice of the comparator. If results from the NCIC-CTG cohort prove similar to our original analysis of the US NCI RCTs, we will corroborate that "equipoise hypothesis" predicts treatment success in RCTs. This in turn will provide a strong rationale to pursue the analysis of industry-sponsored RCTs. The results from this proposal will result in tangible short-term and long-term benefits for all parties involved in clinical research (patients, researchers and policy-makers), who are naturally interested in knowing how many new treatments can be discovered as a proportion of the overall testing in clinical trials. In addition, the results generated from aim #2, will also enhance the public trust in the RCT system, which has been seriously undermined in recent years. Any findings indicating potential compromise in integrity of clinical trial system will provide the basis for instantaneous corrective actions (e.g. improving particular methodological deficiency, correcting for publication bias etc) resulting in the immediate practical application of our research. Understanding the "research payback" and how treatment success and ethics are closely mtertwined is of the crucial importance for maintaining the viability of the entire clinical trial system. The public will continue to support the clinical trial system only if it finds that these studies have produced acceptable rate of successful results that are credible and of high quality without compromised research integrity.